Skip to main content

Is heme iron intake associated with risk of coronary heart disease? A meta-analysis of prospective studies

European Journal of Nutrition volume 53, pages 395–400 (2014)Cite this article

Abstract

Purpose

Heme iron may contribute to the development of atherosclerosis by catalyzing production of hydroxyl-free radicals and promoting low-density lipoprotein oxidation. However, epidemiologic findings regarding the association between heme iron intake and risk of coronary heart disease (CHD) are inconsistent. We aimed to investigate the association by carrying out a meta-analysis of prospective studies.

Methods

Relevant studies were identified by using PubMed and EMBASE databases between January 1966 and April 2013 and also by manually reviewing the reference lists of retrieved publications. Summary relative risks (RRs) with corresponding 95 % confidence intervals (CIs) were computed using a random-effects model.

Results

Six prospective studies, which contained a total of 131,553 participants and 2,459 CHD cases, met the inclusion criteria. Combined results indicated that participants with higher heme iron intake had a 31 % increased risk of CHD, compared with those with lower intake (RR = 1.31, 95 % CI 1.04–1.67), with significant heterogeneity (P heterogeneity = 0.05, I 2 = 55.0 %). Excluding the only study from Japan (limiting to Western studies) yielded a RR of 1.46 (95 % CI 1.21–1.76), with no study heterogeneity (P heterogeneity = 0.44, I 2 = 0.0 %). The dose–response RR of CHD for an increase in heme iron intake of 1 mg/day was 1.27 (95 % CI 1.10–1.47), with low heterogeneity (P heterogeneity = 0.25, I 2 = 25.8 %). We observed no significant publication bias.

Conclusions

This meta-analysis suggests that heme iron intake was associated with an increased risk of CHD.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. de Valk B, Marx JJ (1999) Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 159:1542–1548

    Article  Google Scholar 

  2. Sullivan JL (1981) Iron and the sex difference in heart disease risk. Lancet 1:1293–1294

    CAS  Article  Google Scholar 

  3. Gupta R, Rastogi S, Nagar R, Kastia S, Kaul V (2000) Dietary and serum iron, body iron stores and coronary heart disease. J Assoc Physicians India 48:489–492

    CAS  Google Scholar 

  4. Reunanen A, Takkunen H, Knekt P, Seppanen R, Aromaa A (1995) Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 238:223–230

    CAS  Article  Google Scholar 

  5. Tavani A, Gallus S, Bosetti C, Parpinel M, Negri E, La Vecchia C (2006) Dietary iron intake and risk of non-fatal acute myocardial infarction. Public Health Nutr 9:480–484

    Google Scholar 

  6. Ascherio A, Willett WC, Rimm EB, Giovannucci EL, Stampfer MJ (1994) Dietary iron intake and risk of coronary disease among men. Circulation 89:969–974

    CAS  Article  Google Scholar 

  7. Casiglia E, Tikhonoff V, Bascelli A, Giordano N, Caffi S, Andreatta E, Mazza A, Boschetti G, Grasselli C, Saugo M, Rigoni G, Spinella P, Palatini P (2011) Dietary iron intake and cardiovascular outcome in Italian women: 10-year follow-up. J Womens Health (Larchmt) 20:1565–1571

    Article  Google Scholar 

  8. Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, Boeing H, Hofman A, Witteman JC (1999) Dietary iron and risk of myocardial infarction in the Rotterdam study. Am J Epidemiol 149:421–428

    CAS  Article  Google Scholar 

  9. Qi L, van Dam RM, Rexrode K, Hu FB (2007) Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes Care 30:101–106

    CAS  Article  Google Scholar 

  10. van der A DL, Peeters PH, Grobbee DE, Marx JJ, van der Schouw YT (2005) Dietary haem iron and coronary heart disease in women. Eur Heart J 26:257–262

    CAS  Article  Google Scholar 

  11. Zhang W, Iso H, Ohira T, Date OC, Tanabe N, Kikuchi S, Tamakoshi A (2012) Associations of dietary iron intake with mortality from cardiovascular disease: the JACC study. J Epidemiol 22:484–493

    Article  Google Scholar 

  12. Cook JD (1990) Adaptation in iron metabolism. Am J Clin Nutr 51:301–308

    CAS  Google Scholar 

  13. Carpenter CE, Mahoney AW (1992) Contributions of heme and nonheme iron to human nutrition. Crit Rev Food Sci Nutr 31:333–367

    CAS  Article  Google Scholar 

  14. Hambraeus L (1999) Animal- and plant-food-based diets and iron status: benefits and costs. Proc Nutr Soc 58:235–242

    CAS  Article  Google Scholar 

  15. de Oliveira Otto MC, Alonso A, Lee DH, Delclos GL, Bertoni AG, Jiang R, Lima JA, Symanski E, Jacobs DR Jr, Nettleton JA (2012) Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease. J Nutr 142:526–533

    Article  Google Scholar 

  16. Lee DH, Folsom AR, Jacobs DR Jr (2005) Iron, zinc, and alcohol consumption and mortality from cardiovascular diseases: the Iowa Women’s Health Study. Am J Clin Nutr 81:787–791

    CAS  Google Scholar 

  17. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    CAS  Article  Google Scholar 

  18. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  Google Scholar 

  19. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  Article  Google Scholar 

  20. Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309

    CAS  Google Scholar 

  21. Orsini N, Bellocco R, Greenland S (2006) Generalized least squares for trend estimation of summarized dose-response data. Stata J 6:40–57

    Google Scholar 

  22. Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, Yamaji T, Takachi R, Tsugane S (2012) Zinc and heme iron intakes and risk of colorectal cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 96:864–873

    CAS  Article  Google Scholar 

  23. Sun Q, Shi L, Rimm EB, Giovannucci EL, Hu FB, Manson JE, Rexrode KM (2011) Vitamin D intake and risk of cardiovascular disease in US men and women. Am J Clin Nutr 94:534–542

    CAS  Article  Google Scholar 

  24. Kromhout D (2012) Omega-3 fatty acids and coronary heart disease. The final verdict? Curr Opin Lipidol 23:554–559

    CAS  Article  Google Scholar 

  25. Tappel A (2007) Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. Med Hypotheses 68:562–564

    CAS  Article  Google Scholar 

  26. de Oliveira Otto MC, Alonso A, Lee DH, Delclos GL, Jenny NS, Jiang R, Lima JA, Symanski E, Jacobs DR Jr, Nettleton JA (2011) Dietary micronutrient intakes are associated with markers of inflammation but not with markers of subclinical atherosclerosis. J Nutr 141:1508–1515

    Article  Google Scholar 

  27. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291:711–717

    CAS  Article  Google Scholar 

  28. Tzoulaki I, Brown IJ, Chan Q, Van Horn L, Ueshima H, Zhao L, Stamler J, Elliott P (2008) Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study. BMJ 337:a258

    Article  Google Scholar 

  29. Clarke R, Shipley M, Lewington S, Youngman L, Collins R, Marmot M, Peto R (1999) Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol 150:341–353

    CAS  Article  Google Scholar 

  30. Thornton A, Lee P (2000) Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol 53:207–216

    CAS  Article  Google Scholar 

  31. Higgins JP, Green S, Collaboration C (2008) Cochrane handbook for systematic reviews of interventions. Wiley Online Library, United States

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Affiliations

  1. Department of Cardiothoracic Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China

    Wei Yang, Bin Li, Xiao Dong, Xiao-Qiang Zhang, Yuan Zeng, Jian-Liang Zhou, Yan-Hua Tang & Jian-Jun Xu

Authors
  1. Wei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Qiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian-Liang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan-Hua Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-Jun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao Dong.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, W., Li, B., Dong, X. et al. Is heme iron intake associated with risk of coronary heart disease? A meta-analysis of prospective studies. Eur J Nutr 53, 395–400 (2014). https://doi.org/10.1007/s00394-013-0535-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-013-0535-5

Keywords

  • Heme iron
  • Prospective studies
  • Coronary heart disease
  • Meta-analysis